打字猴:1.700638369e+09
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1700638370 目前基因治疗的研究虽然有较大进展,还有许多问题尚未解决。首先,人类目前所知的与疾病有关的基因还很不充分,对许多疾病的遗传背景了解不够,故基因治疗的应用受到极大的限制;其次,目前所采用的载体系统在导入效率、靶向性、载体容量及宿主反应等方面各有优缺点,缺乏各方面都较优良的载体;第三,在导入基因表达水平的调控方面还缺乏有效手段;第四,将治疗基因和载体导入体内必须考虑其潜在的危险性如:细胞原癌基因的激活、抗癌基因的失活、细胞DNA错配修复系统被干扰、野生型病毒再感染细胞而互补激活缺陷的重组病毒载体;刺激机体对基因修饰的靶细胞进行免疫反应;治疗基因产物所产生的非期望的细胞毒性反应等安全问题还有待于进一步研究。此外,基因治疗还有许多伦理问题。虽然体细胞基因治疗已获得社会伦理的认同,但社会和医学将对这一方法进行有关安全的控制,以不伤害患者、医务人员、病人家属和公众为基本要求。
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1700638372 尽管现代医学已经取得许多令人瞩目的成就,但许多疾病如肿瘤、持续性病毒感染、某些遗传性疾病等的治疗效果仍有非常不理想。各国学者都寄希望于这一技术将来能在上述“难治性疾病”的治疗方面发挥重要作用。目前,美国已经批准了数百项基因治疗项目进入临床研究,其中部分研究已取得了较好的结果,显示出令人鼓舞的前景。我国这方面研究的起步虽然较晚,但相信在广大医务工作者和分子生物学工作者的共同努力下,一定会赶超国际先进水平,为人类健康事业作出贡献。
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1700638374 【思考题】
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1700638376 1.试述基因诊断的优越性及其应用前景。
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1700638378 2.试述RNAi在内科学研究中的应用价值。
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1700638380 参考文献
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1700638382 [1] Prusiner SB. Prion diseases and the BSE crisis. Science, 1997, 278:245-251.
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1700638384 [2] Hannon GJ. RNA interference. Nature, 2002, 418:244-251.
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1700638386 [3] Barajas M, Mazzolini G, Genove G, et al. Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12. Hepatology, 2001, 33(1):52-61.
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1700638388 [4] Lehmann TG, Wheeler MD, Schwabe RF, et al. Gene delivery of Cu/Zn-superoxide dismutase improves graft function after transplantation of fatty livers in the rat. Hepatology, 2000, 32(6):1255-1264.
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1700638390 [5] Tokunaga T, Abe Y, Tsuchida T, et al. Ribozyme mediated cleavage of cell-associated isoform of vascular endothelial growth factor inhibits liver metastasis of a pancreatic cancer cell line. Int J Oncol, 2002, 21(5):1027-1032.
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1700638392 [6] Liu YP, Haasnoot J, Brake O, et al. Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron. Nucleic Acids Res, 2008, 36(9):2811-2824.
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1700638394 [7] Csorba T, Bovi A, Dalmay T, et al. The p122 subunit of tobacco mosaic virus replicase is a potent silencing suppressor and compromises both small interfering RNA- and MicroRNA-mediated pathways. J Virol, 2007, 81(21):11768-11780.
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1700638396 (陈智 彭国平)
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1700638401 内科学新进展 [:1700627044]
1700638402 内科学新进展 第十四章 核素功能分子影像技术 在内科疾病诊断中的应用
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1700638404 摘 要 核素显像是显示放射性核素标记的放射性药物在体内的分布图。放射性药物根据自己的代谢和生物学特性,能特异地分布于体内特定的器官或病变组织,标记在放射性药物分子上的放射性核素由于发出射线能在体外被探测,因而核素显像是显示器官及病变组织的解剖结构和代谢、功能相结合的显像,而有别于常规的影像学方法。随着放射性药物及显像设备的发展,特别是SPECT、正电子发射断层摄影(positron emission tomography, PET)或PET/CT的出现,核素显像在临床疾病的诊断和研究中发挥着重要的作用。现就部分应用与进展阐述如下。
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1700638406 Abstract Radionuclide imaging is about the profile of radio-pharmaceutical in vivo. Radio-pharmaceutical could be distributed to the specified organ or the tissue with pathological changes according to its characteristic of metabolism and biology. The rays emitted by radioisotope which is labeled on radioactive drug can be detected in vitro, so radionuclide imaging could provide not only anatomic structure but also information about metabolism and function of the organ or the tissue. Obviously it is different from conventional imageology. At present, radionuclide image is widely used in not only clinical procedures but also in scientific studies. For example, in cardiovascular system, radionuclide image is widely used in diagnosis, for instruction of clinical therapy and providing information about dangerous of disease and evaluating prognosis of cardiovascular disease; in oncology, it can offer information from point view of metabolism which made early diagnosis of tumor easy, monitor curative effect, differentiate recrudescence form scar which is different by CT technology and identify malignant or benign tumor; in nervous system, it is used in study of higher brain function in addition to diseases; in organ transplantation, the activity of transplanted organ could be monitored by radionuclide image; in the investigation of infection and inflammation, it is also useful. On the whole, with the development of radioactive drug and visualization equipment, particularly the SPECT and PET(positron emission tomography, PET)or PET/CT, radionuclide imaging plays more and more important role in diagnosis and research of clinical disease. Now we’ll present some application and development of radionuclide image as follows.
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1700638411 内科学新进展 [:1700627045]
1700638412 内科学新进展 第一节 在心血管疾病中的应用
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1700638414 目前,核素显像不仅用于心血管疾病的诊断,更重要的是用于指导临床治疗和提供疾病危险程度及预后的评估。临床应用主要有三个方面:一是应用不同的心肌灌注显像剂评价冠状动脉的灌注;二是应用门控心血池显像或首次通过研究估计心室的泵功能;三是诊断和评价心肌梗死。现仅对心肌灌注显像、心肌细胞活力测定及粥样斑块显像三方面的进展作一介绍。
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1700638416 一、心肌灌注显像
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1700638418 心肌灌注显像(myocardial perfusion imaging)是心肌显像中最常用的一种。心肌灌注显像最有价值的临床应用是与负荷试验相结合评价缺血性心脏病,它可以获得比其他诊断方法更有价值的重要信息,特别是疾病预后的信息。目前用于心肌灌注显像的药物较多,常用的单光子发射显像的显像剂有201Tl和99mTc甲氧基异丁基异腈(99mTc-sestamibi, 简称99mTc-MIBI)等。近年来随着新的显像剂研究进展,一些新的99mTc标记药物如99mTc-tetrofosmin(P53, 1, 2双 [双(2乙氧乙基)膦] 乙烷)、99mTc-teboroxime已开始用于临床。此外,应用PET进行心肌灌注显像时,需用正电子发射的显像剂如82Rb、13N-NH3和15O-H2O等。不同的显像剂其生物学特性、显像方法及临床价值有一定差别。其主要应用于临床急、慢性冠心病的诊断、危险性分级、评价预后及疗效评估等。
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